Research Projects

On-going faculty research projects for students

Dr. Glen Livesay, ongoing project research with collagen

Development and analysis of collagenous biomaterials for soft tissue engineering

The abundance and structural importance of collagen in the body make this biomaterial a logical choice for the development of a broad spectrum of tissue engineering applications. The relative biocompatibility of collagen has motivated many researchers to culture cells within collagen gels to create soft ti ssue equivalents in vitro. However, many of these efforts have met with limited success because the constituent cells dramatically contract the gels over time - resulting in a construct which is only a fraction of the original size, and containing a population of cells that has suff ered a large degree of apoptosis. To address these problems, an approach from the field of composite materials is being utilized, wherein the inclusion of short fibers (aspect ratio greater than 10, but not continuous) within a matrix enables the modulation of overall composite properties with relatively minimal increases in material fabrication complexity. The composite materials consist of type I collagen fibers embedded in Type I collagen gels. Long continuous fibers placed within the composites (when desired) alter the tensile tangent modulus of the constructs; the gel phase of the composites is hospitable to cell culture. Recent work at Rose-Hulman developed new techniques to produce collagen fibers with specified cross-sectional areas and shapes, and provided the first experimental data on collagen gel-fiber mechanical interactions.

This past year, work focused on characterizing and selectively controlling mechanical properties of collagen fibers, gels, and fiber/gel composites.

Student presents collagen findings

Recently a set of long term, in vitro, factorial-design experiments concluded that quantitatively explored the effects of: included fiber size, total fiber mass, the inclusion of macropores within our composite biomaterials, and the application of a periodic compressive mechanical stimulus, on a number of biomaterial aspects (including: composite compressive modulus, constitutent cell viability, and cellular production of glycosaminoglycan, elastin, and matrix metalloprotease). The largest, mechanically-sound, biologically-viable cell/composite constructs to the knowledge in the field to date has been constructed. A recent discovery that pre-chondrocytes behave differently in our collagen composite biomaterials than do pre-adipocytes, osteoblasts, or fibroblasts was identified. This work implies that expensive continuous-sti r bioreactors (the standard in the field) for cartilage tissue engineering may not be necessary. Currently the eff ects of strategically varying key parameters of our collagen fiber preparation protocol are being explored by seeking improved mechanical strength, greater fiber-gel interactions, and the characteristic nonlinear stress/strain behavior observed in natural collagenous tissues.

An examination of virus species and their zoonotic transmission among amphibians

In recent years, many viruses (such as Hantaviruses and SARS coronavirus) have emerged in the human population. The emergence of these new viruses has focused much attention on the monitoring of viruses and their diseases. Even with all this focus, the scientific community is unable to predict when and if a new virus will emerge. The focus of this research is to employ the techniques of molecular biology to probe for viruses in nature and to examine their patterns of emergence. Amphibians serve as a good model to study the emergence of viruses because the amphibian population has been declining globally and at least one family of viruses, the iridoviruses, has been implicated in mass die-off s worldwide. It is important to search for other potential viral disease threats prior to their emergence in the amphibian population. This study seeks to investigate the emergence of viral diseases in amphibians by tracking the prevalence and transmission of viruses in amphibian populations. Specifically, iridoviruses are monitored using PCR-based methods in local (Vigo County, IN) amphibian populations. In addition, viruses that have yet to be discovered in the same populations will be identified using a PCR-based method using degenerative primers.

The strategies used by men and women to choose relationship partners have developed in our evolutionary history, and reflect the constraints and needs of attracting, acquiring, maintaining, and protecting mating relationships. Further, elements of the current environment present novel challenges to our suite of evolved behaviors. Research on these issues seeks to elucidate both historical influences on mate choice and which novel elements have the most significant influence on mate choice patterns. A variety of research strategies are applied to these questions - surveys and data-gathering from both males and females, alternate analysis of existing data, and mathematical modeling. Recent lessons learned include that RHIT men with girlfriends are taller than men without girlfriends, but the two groups were similar in other biometrics and their likelihood of participating in varsity sports, and that students as participants in sexual selection research have different interpretations than do researchers of adjectives used to describe behavioral traits. Both of these lessons are appropriate for further investigation.

Biochemical characterization of plant disease defense mechanisms

Unlike animals, which have evolved an elaborate immune system for recognizing general pathogen invasion, plants have developed an extensive surveillance system that can recognize specific pathogen gene products. In this so-called "gene-for-gene" resistance, the products of specifi plant-derived genes (known as resistance, or "R" proteins) recognize the products of specific pathogen genes (known as avirulence "avr", or effector molecules) and signal downstream defense responses in the plant. NDR1 (non-race specific disease resistance) is a gene in Arabidopsis thaliana that is required for disease resistance mediated by at least three different resistance genes. As a result, plants that lack a functional copy of NDR1 are susceptible to a range of pathogens. Despite the crucial role of NDR1 in disease resistance, litt le is known about the molecular function of NDR1. Recent evidence suggests NDR1 exists in a complex with other disease resistance proteins at the plasma membrane. The composition of this protein complex, as well as its dynamics during infection, is not yet known. The primary goal of this research is to understand the role of NDR1 in disease resistance, including its interaction with plant and pathogen proteins during infection. Current research activities include site-directed mutagenesis of putati ve functi onal domains, and mutant screens for dominant suppressors of NDR1. Furthermore, there are a number of Arabidopsis sequences that have high similarity (>60%) to NDR1. Until recently, it was thought that these sequences were non-functional pseudogenes. Recent RT-PCR data indicate that at least two of these genes, tentatively called "NDR2" and "NDR3" are expressed in planta. Through epitopetagging and over-expression experiments, whether NDR2 and NDR3 encode functional proteins and participate in bacterial disease resistance is being investigated. The knowledge gained from this research, including the cloning and characterization of novel disease resistance genes, will help elucidate the molecular basis of disease resistance and contribute to the general understanding of the biochemical signaling events involved in resistance pathways.